Structural and Dynamic Alteration of Glycated Human Serum Albumin in Schiff Base and Amadori Adducts: A Molecular Simulation Study

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  • Sittiwanichai, Sirin
    Faculty of Science, Department of Chemistry, Kasetsart University
  • Japrung, Deanpen
    National Nanotechnology Center, National Science and Technology Development Agency
  • 森, 俊文
    九州大学先導物質化学研究所 九州大学大学院総合理工学府
  • Pongprayoon, Prapasiri
    Faculty of Science, Department of Chemistry, Kasetsart University Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, KU Institute for Advanced Studies, Kasetsart University

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説明

Human serum albumin (HSA) is a protein carrier in blood transporting metabolites and drugs. Glycated HSA (GHSA) acts as a potential biomarker for diabetes. Thus, many attempts have been made to detect GHSA. Glycation was reported to damage the structure and ligand binding capability, where no molecular detail is available. Recently, the crystal structure of GHSA has been solved, where two glucose isomers (pyranose/ GLC and open-chain/GLO) are located at Sudlow’s site I. GLO was found to covalently bind to K_195, while GLC is trapped by noncontact interactions. GHSA exists in two forms (Schiff base (SCH) and Amadori (AMA) adducts), but how both disrupt albumin activity microscopically remains unknown. To this end, molecular dynamics simulations were performed here to explore the nature of SCH and AMA. Both forms are found to alter the main protein dynamics, resulting in (i) the widening of Sudlow’s site I entrance, (ii) the size reduction of nine fatty acid-binding pockets, (iii) the enlargement of Sudlow’s site I and the shrinking of Sudlow’s site II, (iv) the enhancement of C_34 reactivity, and (v) the change in the W_214 microenvironment. These unique characteristics found here can be useful for understanding the effect of glycation on the albumin function in more detail and designing specific and selective GHSA detection strategies.

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詳細情報 詳細情報について

  • CRID
    1050018971027969792
  • NII書誌ID
    AA11114073
  • ISSN
    15205207
    15206106
  • HANDLE
    2324/7159643
  • 本文言語コード
    en
  • 資料種別
    journal article
  • データソース種別
    • IRDB

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